Metabolic Syndrome

The term equine metabolic syndrome (EMS) has only been in use
for the last 10 years and replaces previous terms such as
peripheral Cushing's syndrome, Cushings X and pre-laminitic
metabolic syndrome. The term describes a common syndrome of obesity
and predisposition to laminitis that affects horses and in
particular ponies. The condition has similarities with human
metabolic syndrome and Type II Diabetes.

Aetiopathogenesis

A reduction in the normal response to insulin (insulin
resistance) is central to EMS. Insulin's most important function is
the control of glucose levels in the blood and when insulin
resistance occurs the normal relationship between insulin and
glucose levels becomes disrupted. In addition to insulin resistance
the syndrome also encompasses a number of other potential metabolic
derangements including altered energy metabolism, changes in fat
composition, clotting disorders, inflammation and damage to blood
vessels. In horses the blood vessels in the feet are thought to be
especially susceptible to these metabolic changes as a result of
their unique anatomy potentially giving rise to laminitis. The
precise mechanisms by which insulin resistance and other metabolic
changes result in disease in the feet are complex and not fully
understood; however possibilities include dysfunction of the cells
lining the blood vessels of the foot, constriction of the blood
vessels, reduced glucose uptake in the foot, altered function of
the cells that produce hoof horn, and increased activity of
potentially damaging enzymes called matrix metalloproteinases.

Certain breeds have been recognised to be at greater risk of EMS
including Welsh, Dartmoor and Shetland ponies and Morgan, Arabian
and Warmblood horses. Any breed can be affected if management and
particularly diet are inappropriate. Furthermore, this is a disease
induced by diet and management factors and can be prevented in all
breeds with appropriate dietary restriction.

Clinical signs

Obesity is the classical sign of EMS
and may be generalised (Figure 1) or localised. Common sites of
regional fat deposition are surrounding the nuchal ligament in the
neck or "cresty neck" (Figure 2), around the tail head, behind the
shoulder, around the eyes (Figure 3) and in the prepuce or mammary
gland region. The absence of obesity does not rule out the presence
of the condition, occasionally horses that appear to be lean may
have insulin resistance and other changes characteristic of
EMS.

Figure 1: Obesity: a characteristic sign of
EMS

Figure 2: Cresty neck in a pony with
EMS

Figure 3: Excessive fat deposition around the
eye in a pony with EMS

Lameness and evidence of current or
previous laminitis may be present.
Indicators of laminitis include poor horn quality, uneven or
divergent growth rings on the hooves (Figure 4), flat or convex
soles (Figure 5), divergent white lines, bruising of the white line
and chronic foot infections.

Figure 5: The convex sole of a pony with EMS
and chronic laminitis

Abnormal cycling may be observed in
mares. This is uncommon but mares may lose their seasonal
anovulatory period and have prolonged interovulatory periods.

Equine metabolic syndrome is often confused with Equine
Cushing's Disease or more correctly, Pituitary Pars Intermedia
Dysfunction (PPID). Although these two diseases have different
causes they may both result in insulin resistance and laminitis.
There are however important differences:

EMS horses are typically young or middle aged, horses with PPID
are generally in their teens or older

Horses with PPID may demonstrate delayed or failed shedding of
the winter haircoat, excessive sweating, increased thirst,
increased urination, muscle wasting and a number of other signs
that are not seen with EMS.

Horses with PPID have abnormal pituitary gland function; horses
with EMS do not.

Diagnosis

A presumptive diagnosis can often be made from the appearance of
the horse (overweight) and a history of laminitis. In order to
confirm the presence of EMS insulin resistance has to be
identified. This can be done in a number of ways but whichever
testing method is used it is important that the horse is starved
prior to testing and is not painful or stressed at the time of
testing. Therefore, testing should not be performed when a horse
develops an episode of painful laminitis.

Testing methods include:

Single blood samples for insulin and glucose
concentrations. These results can also be used to
calculate "proxies" which estimate the risk of laminitis
developing. Insulin should be less than 20 iu/ml in normal horses
but some horses with EMS will also have normal levels making the
single blood tests slightly unreliable and prompting the use of
more accurate tests of insulin function in these cases. In most
horses, glucose stays within the normal range so on its own it is
not reliable for diagnosis.

AnOral Glucose Challenge Test
assesses the insulin response to a meal of glucose and is therefore
more accurate than a single blood test. A blood test is performed
(usually 2 hours) after the horse is fed glucose and the resulting
insulin concentration is measured.

Intravenous glucose and insulin tests
are considered to be the most accurate but are also the most
involved and therefore the most expensive. Glucose and insulin are
usually administered together and the horse's glucose and insulin
responses to them are measured over the next few hours. Because
samples have to be taken frequently an intravenous catheter is
generally placed and the tests are generally performed in a
veterinary hospital.

Blood samples may also be useful in identifying increased levels
of fat and hormones other than insulin that are also characteristic
of EMS. Diagnosis of EMS if often dependent upon specific tests to
rule-out PPID as a cause of insulin resistance.

Radiographs may be taken to confirm the presence of laminitis
and to determine the severity of any structural changes that may
have occurred in the feet.

Prevention and Treatment

The principles of prevention and treatment are very
straightforward; dietary restriction and exercise. Not only do
these measures result in weight loss but also increased fitness
which improves the way the body responds to insulin. Horses have
evolved to lose weight annually through the winter and preventing
this from happening is damaging to the metabolism and results in
EMS. Horses with, or at risk of, EMS should be fed a diet that is
low in soluble sugars and starches. In many cases this means
feeding forage with a high fibre and low sugar level only; most
native breeds do not require hard feed to maintain their condition.
Access to pasture should also be limited especially when grass is
lush and growing. Sugars will also accumulate when the days are
sunny and the nights are cold in the winter so these periods are
also to be avoided. Some horses with established EMS may not be
able to tolerate any access to pasture.

Horses that have EMS and need to lose weight should be
restricted to a diet of grass hay at 1-2% of their body weight with
all treats eliminated from the diet. More radical dietary
restriction is often necessary but should be done under veterinary
guidance as excessive weight loss over too short a period of time
may result in other metabolic disorders. Provision of a vitamin and
mineral balancer is advisable.

Affected or at risk horses should be exercised as much as
possible. If laminitis develops exercise may not be possible and
this presents major difficulties in management. It is therefore
worth being proactive and tackling the condition before laminitis
occurs. If laminitis does develop, this will need specific
treatment. (See laminitis bulletin).

In humans with metabolic syndrome there are a number of drugs
that are used to increase insulin sensitivity. These have been
tried in horses but results are mixed. Metformin is one such drug
that is popular in the UK but there are concerns over whether it is
absorbed from the intestine and whether it is effective.
Levothyroxine is a thyroid hormone that increases metabolic rate
and in so doing induces weight loss. It is important to realise
that these horses are not deficient in thyroid hormones and that
administration of levothyroxine results in abnormally high levels
of thyroid hormones. Levothyroxine is effective but prohibitively
expensive in most cases.

A number of supplements have been suggested to be of benefit in
horses with EMS including chromium, magnesium, cinnamon, and
chasteberry (Vitex agnus-castus) extract. There is no evidence that
they are beneficial and indeed there is some evidence that they are
ineffective and so currently their use cannot be recommended.

Welfare implications

The welfare implications of laminitis are huge and the majority
of cases in the UK are the result of EMS. Laminitis is one of the
most common reasons for euthanasia of horses in the UK and results
in extensive suffering in animals that survive the condition. Our
desire to keep horses in a fatter condition than they should be and
our reluctance to restrict diet and access to grazing in at-risk
animals directly result in this preventable suffering.

Summary of key learning points

EMS is a syndrome of insulin resistance, risk of laminitis and
in most cases obesity

The condition is preventable

Genetics, diet and exercise influence body fat mass that leads
to the disease

Young to middle age animals are most commonly affected

Ponies and native breeds are at greatest risk

The condition has some similarities with, but is distinct from,
Equine Cushing's Disease

Insulin resistance is diagnosed by blood tests, or preferably,
by assessing the response to glucose administration

The condition is prevented and managed by dietary restriction
and, where laminitis permits, exercise

Drug therapies should be a last resort and are less effective
than management changes

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